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Albiflorin Alleviates Severe Acute Pancreatitis-Associated Liver Injury by Inactivating P38MAPK/NF-κB Signaling Pathway

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Abstract

Albiflorin (Alb) is a monoterpenoid component that is commonly found in Paeonia lactiflora Pall. or Paeonia veitchii Lynch. It is known for its impressive anti-oxidant and anti-inflammatory properties. However, the effect of Alb on severe acute pancreatitis (SAP)-associated liver injury has not been fully understood. To investigate this, we conducted a study using a rat model of SAP induced by administering two intraperitoneal injections of 20% l-arginine (3.3 g/kg) over a period of 2 h. Subsequently, the SAP-induced rats were randomly assigned into different groups with the treatment of gradient doses of Alb (5, 10, and 20 mg/kg), with the normal saline as the sham group. The pathological changes in rat livers were evaluated through hematoxylin–eosin staining. Furthermore, the levels of amylase (AMY), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined using specific enzyme-linked immunosorbent assay kits. Moreover, the serum levels of inflammatory factors, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, were quantified. Finally, immunohistochemical and Western blot analyses were conducted to determine phosphorylation levels of nuclear factor kappa B (NF-κB) p65 and mitogen-associated protein kianse (MAPK) p38 in the liver tissues. TNF-α stimulated liver cells were used as a cell model to further confirm the involvement of NF-κB and p38 in the effect of Alb. Our study revealed that Alb effectively mitigated the hepatic pathological damage in a dose-dependent manner and reduced the levels of indicators associated with hepatic malfunction (AMY, AST, and ALT) in rats with SAP-induced liver injury. Additionally, Alb demonstrated its ability to suppress inflammation and oxidative stress markers in the liver tissues. Alb exerted dose-dependent inhibitory effects by modulating the P38MAPK/NF-κB signaling pathway. Overall, our findings strongly support the hepatoprotective effect of Alb in rats with SAP-induced liver injury, suggesting that Alb protects against SAP-induced liver injury through the suppression of inflammation and oxidative stress via the P38MAPK/NF-κB signaling pathway.

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Data Availability

The datasets used and analyzed during the current study are available from the corresponding author via email request.

Abbreviations

Alb:

Albiflorin

ALT:

Alanine aminotransferase

AMY:

Amylase

AST:

Aspartate aminotransferase

BCA:

Bicinchoninic acid

CCK-8:

Cell count kit-8

DAB:

3,3′-Diaminobenzidine

ELISA:

Enzyme-linked immunosorbent assay

GSH-Px:

Glutathione peroxidase

H&E:

Hematoxylin–eosin

IHC:

Immunohistochemistry

IL:

Interleukin

MAPK:

Mitogen-associated protein kinase

MDA:

Malondialdehyde

NF-κB:

Nuclear factor kappa B

PVDF:

Polyvinylidene difluoride

RIPA:

Radioimmunoprecipitation assay

SAP:

Severe acute pancreatitis

SDS-PAGE:

Dodecyl sulfate–polyacrylamide gel electrophoresis

SOD:

Superoxide dismutase

TNF-α:

Tumor necrosis factor alpha

References

  • Amin A, Lotfy M, Mahmoud-Ghoneim D, Adeghate E, Al-Akhras M, Al-Saadi M, Al-Rahmoun S, Hameed R (2011) (2011) Pancreas-protective effects of chlorella in STZ-induced diabetic animal model: insights into the mechanism. J Diabetes Mellit 1:36–45

    Article  Google Scholar 

  • Bouabdallah S, Al-Maktoum A, Amin A (2023) Steroidal saponins: naturally occurring compounds as inhibitors of the hallmarks of cancer. Cancers (Basel) 15(15):3900

    Article  CAS  PubMed  Google Scholar 

  • Cai Z, Liu J, Bian H, Cai J (2019) Albiflorin alleviates ovalbumin (OVA)-induced pulmonary inflammation in asthmatic mice. Am J Transl Res 11:7300–7309

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chowdhury TT, Salter DM, Bader DL, Lee DA (2008) Signal transduction pathways involving p38 MAPK, JNK, NFkappaB and AP-1 influences the response of chondrocytes cultured in agarose constructs to IL-1beta and dynamic compression. Inflamm Res 57(7):306–313

    Article  CAS  PubMed  Google Scholar 

  • Gliem N, Ammer-Herrmenau C, Ellenrieder V, Neesse A (2021) Management of severe acute pancreatitis: an update. Digestion 102:503–507

    Article  PubMed  Google Scholar 

  • Grimble GK (2007) Adverse gastrointestinal effects of arginine and related amino acids. J Nutr 137(6 Suppl 2):1693S-1701S

    Article  CAS  PubMed  Google Scholar 

  • Habtezion A, Gukovskaya AS, Pandol SJ (2019) Acute pancreatitis: a multifaceted set of organelle and cellular interactions. Gastroenterology 156:1941–1950

    Article  CAS  PubMed  Google Scholar 

  • Hamza AA, Mohamed MG, Lashin FM et al (2020) Dandelion prevents liver fibrosis, inflammatory response, and oxidative stress in rats. JoBAZ 81:43

    Article  Google Scholar 

  • Hamza AA, Heeba GH, Hassanin SO, Elwy HM, Bekhit AA, Amin A (2023) Hibiscus-cisplatin combination treatment decreases liver toxicity in rats while increasing toxicity in lung cancer cells via oxidative stress-apoptosis pathway. Biomed Pharmacother 165:115148

    Article  CAS  PubMed  Google Scholar 

  • Kim JH, Kim M, Hong S, Kim EY, Lee H, Jung HS, Sohn Y (2021) Albiflorin promotes osteoblast differentiation and healing of rat femoral fractures through enhancing BMP-2/Smad and Wnt/beta-catenin signaling. Front Pharmacol 12:690113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Komara NL, Paragomi P, Greer PJ, Wilson AS, Breze C, Papachristou GI, Whitcomb DC (2020) Severe acute pancreatitis: capillary permeability model linking systemic inflammation to multiorgan failure. Am J Physiol Gastrointest Liver Physiol 319:G573–G583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koppelmann T, Pollak Y, Mogilner J, Bejar J, Coran AG, Sukhotnik I (2012) Dietary l-arginine supplementation reduces methotrexate-induced intestinal mucosal injury in rat. BMC Gastroenterol 12:41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lam P, Cheung F, Tan HY, Wang N, Yuen MF, Feng Y (2016) Hepatoprotective effects of Chinese medicinal herbs: a focus on anti-inflammatory and anti-oxidative activities. Int J Mol Sci 17(4):465

    Article  PubMed  PubMed Central  Google Scholar 

  • Li KC, Ho YL, Huang GJ, Chang YS (2015) Anti-oxidative and anti-inflammatory effects of Lobelia chinensis in vitro and in vivo. Am J Chin Med 43(2):269–287

    Article  PubMed  Google Scholar 

  • Li T, Wu YN, Wang H, Ma JY, Zhai SS, Duan J (2020) Dapk1 improves inflammation, oxidative stress and autophagy in LPS-induced acute lung injury via p38MAPK/NF-kappaB signaling pathway. Mol Immunol 120:13–22

    Article  CAS  PubMed  Google Scholar 

  • Liu W, Du JJ, Li ZH, Zhang XY, Zuo HD (2021) Liver injury associated with acute pancreatitis: the current status of clinical evaluation and involved mechanisms. World J Clin Cases 9:10418–10429

    Article  PubMed  PubMed Central  Google Scholar 

  • Lozon L, Saleh E, Menon V, Ramadan WS, Amin A, El-Awady R (2022) Effect of safranal on the response of cancer cells to topoisomerase I inhibitors: does sequence matter? Front Pharmacol 13:938471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma X, Song M, Yan Y, Ren G, Hou J, Qin G, Wang W, Li Z (2021) Albiflorin alleviates cognitive dysfunction in STZ-induced rats. Aging 13:18287–18297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma A, Zou F, Zhang R, Zhao X (2022) The effects and underlying mechanisms of medicine and food homologous flowers on the prevention and treatment of related diseases. J Food Biochem 46(12):e14430

    Article  CAS  PubMed  Google Scholar 

  • Ning W, Wang Y, Zhang F, Wang H, Wang F, Wang X, Tang H, Liang S, Shi X, Liu Z (2013) Beneficial effects of trypsin inhibitors derived from a spider venom peptide in l-arginine-induced severe acute pancreatitis in mice. PLoS ONE 8:e61049

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Pfingstgraf IO, Taulescu M, Pop RM, Orăsan R, Vlase L, Uifalean A, Todea D, Alexescu T, Toma C, Pârvu AE (2021) Protective effects of Taraxacum officinale L. (Dandelion) root extract in experimental acute on chronic liver failure. Antioxidants (Basel) 10(4):504

    Article  CAS  PubMed  Google Scholar 

  • Pirillo A, Casula M, Olmastroni E, Norata GD, Catapano AL (2021) Global epidemiology of dyslipidaemias. Nat Rev Cardiol 18:689–700

    Article  CAS  PubMed  Google Scholar 

  • Portelli M, Jones CD (2017) Severe acute pancreatitis: pathogenesis, diagnosis and surgical management. Hepatobiliary Pancreat Dis Int: HBPD 16:155–159

    Article  CAS  Google Scholar 

  • Salian VS, Wright JA, Vedell PT, Nair S, Li C, Kandimalla M, Tang X, Carmona Porquera EM, Kalari KR, Kandimalla KK (2021) COVID-19 transmission, current treatment, and future therapeutic strategies. Am J Physiol Cell Physiol 18:754–771

    CAS  Google Scholar 

  • Song Y, Wang Y, Qi X, Kang X, Da-Huang-Fu-Zi-Tang LuX (2021) Ameliorates severe acute pancreatitis by elevation of M2 Kupffer cells in rats. Evid-Based Complement Altern Med. https://doi.org/10.1155/2021/5561216

    Article  Google Scholar 

  • Su Z, Wu F (2020) Inflammatory factors induce thrombosis through the miR-146b-3p/p38MAPK/COX-2 pathway. Biomed Res Int 2020:8718321

    Article  PubMed  PubMed Central  Google Scholar 

  • Sugaya A, Suzuki T, Sugaya E, Yuyama N, Yasuda K, Tsuda T (1991) Inhibitory effect of peony root extract on pentylenetetrazol-induced EEG power spectrum changes and extracellular calcium concentration changes in rat cerebral cortex. J Ethnopharmacol 33:159–167

    Article  CAS  PubMed  Google Scholar 

  • Sun J, Li X, Jiao K, Zhai Z, Sun D (2019) Albiflorin inhibits the formation of THP-1-derived foam cells through the LOX-1/NF-kappaB pathway. Minerva Med 110:107–114

    Article  PubMed  Google Scholar 

  • Wang X, Zhang C, Zheng M, Gao F, Zhang J, Liu F (2019) Metabolomics analysis of l-arginine induced gastrointestinal motility disorder in rats using UPLC-MS after magnolol treatment. Front Pharmacol 10:183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Su L, Tan J, Ding T, Yue Y (2023) Albiflorin alleviates DSS-induced ulcerative colitis in mice by reducing inflammation and oxidative stress. Iran J Basic Med Sci 26(1):48–56

    PubMed  PubMed Central  Google Scholar 

  • Xie Y, Mu C, Kazybay B, Sun Q, Kutzhanova A, Nazarbek G, Xu N, Nurtay L, Wang Q, Amin A, Li X (2021) Network pharmacology and experimental investigation of Rhizoma polygonati extract targeted kinase with herbzyme activity for potent drug delivery. Drug Deliv 28(1):2187–2197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu YJ, Mei Y, Shi XQ, Zhang YF, Wang XY, Guan L, Wang Q, Pan HF (2019) Albiflorin ameliorates memory deficits in APP/PS1 transgenic mice via ameliorating mitochondrial dysfunction. Brain Res 1719:113–123

    Article  CAS  PubMed  Google Scholar 

  • Yang AL, McNabb-Baltar J (2020) Hypertriglyceridemia and acute pancreatitis. Pancreatol: Off J Int Assoc Pancreatol 20:795–800

    Article  CAS  Google Scholar 

  • Yang Z, Chang KW, Liu XY, Zhuang L, Wang S, Zheng SS (2021) Liver transplantation for acute-on-chronic liver failure associated with acute necrotizing pancreatitis: a case report. Transpl Proc 53:1303–1307

    Article  Google Scholar 

  • Zhan X, Wan J, Zhang G, Song L, Gui F, Zhang Y, Li Y, Guo J, Dawra RK, Saluja AK, Haddock AN, Zhang L, Bi Y, Ji B (2019) Elevated intracellular trypsin exacerbates acute pancreatitis and chronic pancreatitis in mice. Am J Physiol Gastrointest Liver Physiol 316:G816–G825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang H, Wang J, Lang W, Liu H, Zhang Z, Wu T, Li H, Bai L, Shi Q (2022) Albiflorin ameliorates inflammation and oxidative stress by regulating the NF-kappaB/NLRP3 pathway in Methotrexate-induced enteritis. Int Immunopharmacol 109:108824

    Article  CAS  PubMed  Google Scholar 

  • Zhou X, Fouda S, Zeng XY, Li D, Zhang K, Xu J, Ye JM (2019) Characterization of the therapeutic profile of albiflorin for the metabolic syndrome. Front Pharmacol 10:1151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu L, Zhang D, Yuan C, Ding X, Shang Y, Jiang Y, Zhu G (2017) Anti-Inflammatory and antiviral effects of water-soluble crude extract from Phragmites australis in vitro. Pak J Pharm Sci 30:1357–1362

    CAS  PubMed  Google Scholar 

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Acknowledgements

Not applicable.

Funding

We sincerely acknowledge the funding from the Fuzhou Science and Technology Plan Project (2021-S-157), the National Natural Science Foundation of China (82100687), the Natural Science Foundation of Fujian Province (2023J011357) and the Key Subject Funds of Joint Logistics Support Force (LQZD-XH).

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Author notes

  1. Haitao Li, Xiangpeng Zeng and Dongjie Sun have contributed equally as the first author.

Authors and Affiliations

  1. Department of Gastroenterology, Fuzong Clinical Medical College of Fujian Medical University/The 900th Hospital of the Joint Logistics Support Force Fuzhou, No. 156, West Second Ring Road, Fuzhou City, 350025, Fujian, People’s Republic of China

    Haitao Li, Xiangpeng Zeng, Dongjie Sun & Dazhou Li

  2. Department of Pathology, Fuzong Clinical Medical College of Fujian Medical University/The 900th Hospital of the Joint Logistics Support Force Fuzhou, No. 156, West Second Ring Road, Fuzhou City, 350025, Fujian, People’s Republic of China

    Xingfeng Qi & Wen Wang

  3. Department of Gastroenterology, Fuzhou Second Hospital Affiliated to Xiamen University, No. 47 Shangjidi Road, Cangshan District, Fuzhou City, 350007, Fujian, People’s Republic of China

    Yan Lin

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  1. Haitao Li
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Contributions

WW, HL, YL, XZ, and DS conceived and designed the experiments. HL, XZ, DS, XQ, DL, and WW performed the experiments and wrote the paper. HL, XZ, DS, YL, and XQ analyzed the data. All authors approved the final version of the manuscript as submitted and agreed to be accountable for all aspects of the work.

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Correspondence to Wen Wang or Yan Lin.

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Animal-related experimental procedures gained the approval from the Animal Ethics Committee of Fuzong Clinical Medical College of Fujian Medical University. The experimental protocol followed the relevant guidelines and regulations of the Basel Declaration. The study is reported following ARRIVE guidelines (https://arriveguidelines.org).

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Li, H., Zeng, X., Sun, D. et al. Albiflorin Alleviates Severe Acute Pancreatitis-Associated Liver Injury by Inactivating P38MAPK/NF-κB Signaling Pathway. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10686-9

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